The influence of endogenous and exogenous reproductive hormones on the mammary glands with emphasis on experimental studies in rhesus monkeys.

: Endogenous and exogenous reproductive hormones have long been recognized as a risk factor for breast carcinoma. These hormones are thought to exert their influence by altering the kinetics of cell proliferation, differentiation or atrophy resulting in an increased population of susceptible cells. Prolonged exposure to endogenous hormones (predominantly estrogens and progestins) resulting from either early menarche, late menopause, and absent or reduced ovarian cyclic functions due to parity are associated with an increased risk. Oophorectomy, in contrast, provides a protection inversely related to age at ablation. The influence of exogenous hormones (birth control pills, hormone replacement therapy, etc.) on mammary carcinogenesis remains a controversial issue. The various viewpoints will be discussed. Among rhesus monkeys in captivity, experimental exposure to a variety of synthetic oral contraceptive steroids has resulted in a variety of proliferative changes including atypical hyperplasia and carcinoma in the mammary duct system. A much higher proportion of severe atypias and carcinoma was observed among those receiving progestational hormones in pure form or in combination with estrogens. Pure estrogenic compounds did not cause as severe a proliferation or atypia in as high a proportion as observed when progestational hormones were used in pure or combined form. In view of this finding it is important to use caution when considering addition of progestins to hormone replacement therapy in an effort to prevent endometrial carcinomas. This is particularly important if the patient has other risk factors for breast carcinoma.